A portable application can be run from a removable drive (USB flash drive, iPod, portable hard drive, etc) on any Windows computer without installation.
You will carry the program with settings on removable drive and don't modify settings on host computer.
On Vista and above turn off User Account Control (UAC) or run launcher as admin.

Multi-Users: change Profile by editing ThunderbirdPortable.ini with User=NameOfNewUser
Associated to Firefox Portable if FirefoxPortable and ThunderbirdPortable folders are in the same folder. A link clicked in a mail will be opened in Firefox Portable (don't work on Windows 8 and above).